Selective ion mobility filter

ABSTRACT

Ions with a predetermined ion mobility range are produced by filtering ions entrained in a stream of moving gas with two ion mobility low pass filters located consecutively in the gas stream. Each filter is formed by applying a DC electric field to the gas stream which causes the ions to move in a direction opposite to the gas flow. Ions are collected between the two filters and transferred to a detector or analyzing device. In one embodiment, the maximum field strength of the electric field barrier in the first ion mobility low pass filter is continued as a plateau of essentially constant field strength up to the electric field barrier in the second ion mobility low pass filter, which has a maximum field strength higher that the maximum field strength of the electric field barrier in the first ion mobility low pass filter.

BACKGROUND

The invention relates to the selection of ions of a predetermined rangeof mobilities, preferably for being analyzed by mass spectrometry. Massspectrometers can only ever determine the ratio of the ion mass to thecharge of the ion. Where the terms “mass of an ion” or “ion mass” areused below for simplification, they always refer to the ratio of themass m to the dimensionless number of elementary charges z of the ion.This charge-related mass m/z has the physical dimension of a mass, butit is often also called “mass-to-charge ratio”, although this isincorrect with regard to the physical dimension. The term “ion species”shall denote ions having the same chemical formula, the same charge andthe same three-dimensional structure. Ion species generally comprise allions of an isotope pattern containing ions of slightly different masses,but virtually the same mobilities.

Different kinds of isomers are known for bioorganic molecules: isomersrelated to the primary structure (structural isomers) and isomersrelated to the secondary or tertiary structure (conformational isomers).These isomers have different geometrical forms but exactly the samemass. It is therefore impossible to differentiate between them on thebasis of their mass. Some information as to the structure can beobtained from fragment ion mass spectra; however, an efficient andcertain way to recognize and distinguish such isomers is to separatetheir ions according to their different mobilities.

Nowadays, the mobility of ions is often measured via their driftvelocities in a drift region under the influence of an homogeneouselectric field along the drift region. The drift region is filled withan inert, stationary gas (such as helium, nitrogen or argon). The ionsof the substance under investigation are pulled through the gas by meansof the electric field, which is produced by suitable DC potentialsapplied to ring electrodes arranged along the drift region. The largenumber of collisions with the gas molecules results in a constant driftvelocity v_(d) for each ion species which is proportional to theelectric field strength E: v_(d)=μ×E. The proportionality factor μ iscalled the “ion mobility” of the ion species. The ion mobility μ is afunction of the gas temperature, gas pressure, type of gas, ion chargeand, in particular, the collision cross-section of the ions.

Isomeric ions with the same charge-related mass m/z but differentcollision cross-section have different ion mobilities in a gas of thesame temperature, pressure and type. The Isomer with the smallestgeometric dimension exhibits the greatest mobility compared to otherisomers and therefore the highest drift velocity through the gas.Unfolded protein ions undergo more collisions than tightly foldedproteins. Protein ions which are unfolded or partially folded thereforearrive at the end of the cell later than strongly folded ions of thesame mass. Structural isomers, for example proteins with glycosyl, lipidor phosphoryl groups at different sites, also have different collisioncross-sections, which allow them to be distinguished by measuring theirion mobility.

In chemical and biological research, it has become more and moreimportant to have knowledge about the folding structures of bioorganicions, which can be identified via their mobility. Therefore devices tomeasure the mobility of ions have been incorporated into massspectrometers, in particular, in order to combine the measurements ofthe charge-related mass of ions with the measurement of collisioncross-sections. The folding structures determine the mechanism of actionand thus the function of the molecules in the living organism; differentfoldings can signify normal or abnormal functioning of biopolymers inbiosystems, and hence health or disease of tissue parts or even wholeorganisms.

A number of academic research groups have coupled ion mobilityspectrometers with mass spectrometers. A pressure in the range ofseveral hectopascals has been adopted almost universally in the driftregion; the drift region for higher mobility resolutions measures up tofour meters and more, and electric field strengths of 2,000 volts permeter and more are applied. In this pressure range, the drifting ionsappear to form hardly any complexes with other substances, so themobilities of the ion species can be measured without interferences,unlike mobility measurements at atmospheric pressure. But in the longdrift regions, the ions also diffuse radially over long distances, andtherefore quite large diameters have to be chosen for these driftregions.

The ions are usually introduced into the drift region by pulsing ashutter grid at the entrance of the drift region to form ion clouds,having the shape of thin slices, which are pulled through the driftregion by the electric field. In the gas of the drift region, these ionclouds are subject to diffusion, caused by collisions statisticallydistributed in terms of spatial directions and kinetic energies due tothe molecular Brownian motion. The diffusion takes place in alldirections from the cloud, thus also in radial direction to the driftdirection. The gas in the drift region is sometimes kept at temperaturesof between about 150 and 300 degrees Celsius, but can also be cooleddown for special experiments.

The resolving power of a ion mobility spectrometer is defined asR_(mob)=μ/Δμ=v_(d)/Δv_(d), where Δμ is the width of the ion signal ofthe mobility μ at half height, measured in units of the mobility, andΔv_(d) is the correspondent difference in drift velocity V_(d). Theresolving power R_(mob) is influenced predominantly by the diffusionbroadening of the ion clouds, particularly for long drift regions andhigh electric field strengths; all other influences, such as the spacecharge, tend to be negligibly small.

The part of the resolving power determined by the diffusion broadeningis given by the equation

${R_{d} = \sqrt{\frac{{zeEL}_{d}}{{kT}\;\ln\; 2}}},$where z is the number of unbalanced elementary charges e of the ions, Ethe electric field strength, L_(d) the length of the drift region, k theBoltzmann constant and T the temperature of the gas in the drift region.A high mobility resolution can thus only be achieved by means of highfield strengths E, long drift regions L_(d), or low temperatures T. Thepart R_(d) of the resolving power that is given by the diffusion is notdependent on either the type or pressure of gas in the drift region; themobility K₀ itself, however, does depend not only on the temperature,but also on the pressure and type of gas.

Compared to the numerical values for mass resolutions in massspectrometry, the mobility resolutions which can be achieved in practiceare generally very low. The first commercial ion mobility spectrometerfor bioorganic ions has a mobility resolution of only R_(mob)=40. With amobility resolution of R_(mob)=40, two ion species whose collisioncross-sections differ by only five percent can be well separated intotwo peaks.

Only highly specialized academic working groups have, as yet, been ableto achieve significantly higher mobility resolutions than R_(mob)=100,in rare individual cases up to R_(mob)=200, with long drift lengthsroughly between two and six meters and field strengths between 2,000 and4,000 volts per meter, making it possible to differentiate between ionspecies whose mobilities differ by only one to three percent. Ionmobility spectrometers with a resolution above R_(mob)=100 shall becalled “high resolution” here.

In long mobility drift regions, the transverse diffusion widens the ionclouds broadly. Therefore, longer drift regions must also have a largediameter so that the ions do not touch the enclosure of the driftregion. A well established method is to guide the ions back to the axisof the drift region after they have passed through a part of the driftregion, about two meters, for example. This is done using so-called “ionfunnels”. These consist of a larger number of parallel ring diaphragms,spaced apart from each other in the order of millimeters. The innerdiameter of the diaphragm's aperture taper continuously from thediameter of the drift region, 30 to 40 centimeters, for example, down toa few millimeters and thus form a funnel-shaped enclosed volume. The twophases of an RF voltage, usually of several megahertz and between a fewtens of volts and one hundred volts, are applied alternately to theapertured diaphragms, thus generating a pseudopotential which keeps theions away from the funnel wall. An axial DC voltage gradient issuperimposed on the RF voltage generating a DC electric field along thefunnel. This electric field pushes the ions slowly towards the narrowexit of the funnel and through it. The ion funnel does not measurablyreduce the mobility resolution of a long drift region.

Ion funnels are not only used to guide the ions back to the axis of thedrift regions in ion mobility spectrometers; they are also used in massspectrometers in general to gather the ions from larger ion clouds andto thread these ions into narrow ion guides. Such ion funnels are oftenfound in mass spectrometers with electrospray ion sources; the ionsgenerated outside the vacuum system are transferred, together with acurtain gas, through inlet capillaries into the vacuum system, wherethey are captured by ion funnels and freed of most of the curtain gas.Some mass spectrometers even contain two such ion funnels, placed inseries, in order to move the ions quickly from regions with higherpressure of several hectopascals at the end of the inlet capillary toregions with lower pressure of less than 10⁻² pascal.

High-resolution time-of-flight mass spectrometers with orthogonalinjection of the ions (OTOF-MS), in particular, have proven successfulfor combinations of mobility spectrometers with mass spectrometers. Forsuch combinations, the common high-resolution ion mobility spectrometersof the drift type have the disadvantage of being several meters long.For the construction of small, high-resolution mobility analyzers, onetherefore has to look for a solution which shortens the overall lengthbut does not diminish the mobility resolution.

In document U.S. Pat. No. 7,838,826 B1 (M. A. Park, 2008), an ionmobility spectrometer is presented, the size of which amounts to aboutten centimeters only. It is based upon a gas flow driving ions againstand over an electric counter-field barrier inside a modified ion funnelof a time-of-flight mass spectrometer. Since the publication of thisdevice, ion mobility resolutions in excess of R_(mob)=100 have alreadybeen achieved with this small spectrometer. Considerably higherresolutions can be expected by future improvements.

Ion mobility spectrometers with moving gases and electric barriers dateback to the year 1898, when J. Zeleny published an article entitled “Onthe Ratio of the Velocities of the Two Ions produced in Gases by RontgenRadiation; and on some Related Phenomena”, in Philosophical Magazine,No. 46, pp. 120-154. Zeleny generated ions between two parallel gridsproducing a homogeneous electric field and let a broad laminar flow ofgas pass through the two parallel grids in a direction normal to thegrids, counteracting the electric field produced between the grids. Bychanging the electric field, he could separate ions by their differentmobilities. Since then, several patents and patent applications werepublished, using the principle of gas flows for the measurement of ionmobilities; in most cases, however, driving ions by electric fields ofvarying strengths against a moving gas. For none of these ion mobilityspectrometers, however, resolutions near to R_(mob)=100 have beenreported.

The apparatus of M. A. Park, as described in U.S. Pat. No. 7,838,826 B1,and the potential and field profiles for its operation are schematicallyillustrated in FIGS. 1A to 1D. FIG. 1B shows, how the parts (10) and(12) of a quadrupolar funnel, open to gas movement between theelectrodes, are separated by a closed, tube-like quadrupole device (11)shown in FIG. 1A, which is vertically segmented into slices of thinelectrodes (17, 18) arranged around an axis (denoted as the z-axis) witha circular central opening forming the tube. The electrodes areseparated by insulating material closing the gaps. FIG. 1A shows theshape of the electrodes of the funnel (15, 16) in a direction normal tothe z-axis and the shape of the electrodes that form quadrupole tube(17, 18) in a direction normal to the z-axis, the latter withequipotential lines of the quadrupolar field inside the tube. Adifferential pumping system of a mass spectrometer (not shown),surrounding the ion mobility spectrometer, is designed to cause a gas toflow through the tube of part (11) in a laminar way, so that the gasflow assumes the usual parabolic velocity profile (14). Ions, whichenter the first part (10) of the funnel together with the gas, arecollisionally focused into the axis of the tube.

FIGS. 1C and 1D show different DC potential profiles (22 to 26) alongthe z-axis of the tube, and corresponding barriers E_(z) of the electriccounter field, respectively. The operation of the ion mobilityspectrometer will be described by the sequence in which the DC potentialprofiles are supplied. The operation starts with a filling process. Thesteepest potential profile (22) is generated, producing the highestelectric field barrier, collecting ions of all ion mobilities. The ions(27) are blown by the gas flow against the field barrier and are stoppedthere because they cannot surmount the field barrier. Ions with highmobility gather at the foot of the barrier, ions with low mobilitygather near the summit, as symbolically indicated by the smaller andlarger cross sections of the ions (27). When a suitable number of ionshave been collected, the supply of further ions is stopped; forinstance, by reversing the direction of the DC field within the ionfunnel (10). Then, to acquire a spectrum, the potential profile (22) islowered in height continuously in a scan (28), through potentialprofiles (23) to (26), resulting in a decrease of the electric barrier.During the scan, ions of higher and higher mobilities (smaller andsmaller cross sections) can surmount the decreasing summit of thebarrier, exit the spectrometer and be measured by an ion detector,favorably by a mass spectrometer. The measured ion current curvereflects directly the ion mobility spectrum. This device is denominateda “TIMS”, or “trapped ion mobility spectrometer”.

With this instrument, ion mobility resolution R_(mob) increases withincreasing pressure, at least up to a few hectopascal, with increasinggas flow plus barrier height, and with decreasing scan speed. The deviceturns out to be at least as good as drift tubes of about one to twometers in length with stationary gas as described above.

Because only a moderate amount of ions is trapped in each analyzingcycle, only a limited number of ions of each mobility is available ineach single scan, in most cases not enough for a thorough investigationof ions of a selected mobility in a mass spectrometer, for instance, bythe generation of fragment ion spectra. There is still a need to collectmore ions of a selected mobility, or to produce a constant current ofions with a selected mobility, for example by a mobility filter.

It should be mentioned here, that there are other types of short ionmobility spectrometers using gas flows. Document US 2010/0,090,102 A1(O. Raether et al, 2008) describes, how a freely expanding gas flow froma small opening can be used to drive entrained ions over an electricalbarrier within an ion funnel. In document GB 2473723 A (J. Franzen,2009), an apparatus is presented which generates a supersonic gas flowby a Laval nozzle, the supersonic gas flow driving entrained ions overan electrical barrier. In this case, the supersonic gas flow withentrained ions is not enclosed by any radially confining field,particularly not by an RF multipole field.

SUMMARY

The invention is based on the insight that all ion mobility measuringdevices with electrical forces and counteracting gas flows act either asion mobility high pass or low pass filters, each separating ions bytheir mobilities into those which pass the device and those which areheld back. If an electric force generated by a DC potential profile orby an RF pseudopotential profile drives the ions in the direction of theoriginal ion current from the ion source against a gas flow, a mobilityhigh pass filter for ions with smaller cross sections than a limit isproduced. If the gas flow drives entrained ions in the originaldirection of the ion current against an electrical barrier, either a DCelectric barrier or an RF pseudofield barrier generated by an RFpseudopotential, a mobility low pass filter for ions of larger crosssections than a limit is produced.

In accordance with the principles of the invention, at least twoconsecutive mobility high pass and/or low pass filters are used for theselection (filtering) of ions within a predetermined range of ionmobilities, either for the collection of many of these ions in asuitable volume between the filters, or for the generation of a constantbeam of ions with predetermined mobility passing through the filters.

In a first embodiment of the invention, the gas flows in one directiononly through two mobility filters, thus forming either two ion mobilitylow pass or two ion mobility high pass filters. If the space between thefilters acts as an ion storage volume, e.g. formed by an enveloping RFmultipole field, these filters cause ions within a predetermined rangeof mobilities to collect between the two filters. The ions collectedbetween two consecutive ion mobility low pass filters can be transferredto a detector or an analyzing device, such as a mass spectrometer, bychanging the electric field of at least one of the low pass filter. Itis advantageous to stop ions from entering the region of the mobilityfilters before starting the transfer of the collected ions, for exampleby generating a further electric DC barrier upstream of the firstmobility filter. The collected ions in the selected mobility range mayfinally be investigated in more detail, e.g. by a highly resolvedmobility scan of the second filter, or by transferring these ions to amass spectrometer for the generation and acquisition of fragment ionmass spectra. The two mobility filters are preferably two low passfilters, each formed by electric field barriers, wherein the maximumfield strength of the first field barrier is continued as a plateau ofessentially constant field strength up to the second field barrier. Anion mobility spectrum can be acquired by a repeated collection of ionsof different mobility. The resolution of the mobility spectrum can beadjusted by the difference in field strength between the first andsecond field barrier. By lowering the difference in field strength, onlyions of a narrow mobility range are collected between the filters and,thus, the resolution is increased.

In a second embodiment, the gas flows in the consecutive ion mobilityfilters do not have the same direction, thus producing at least one highpass and at least one low pass filter. If the field strengths and thegas flows are adjusted correctly, ions of a selected range of mobilitiescan pass through both filters, thus forming a continuous current of ionswith selected mobilities. These ions may be further investigated by amass spectrometer, e.g. by acquiring spectra of fragment ions afterapplication of a suitable fragmentation method.

By a common change of the adjustment of the consecutive filters in thesecond embodiment, the mobility range of the passing ions can bescanned.

In certain embodiments of the present invention, RF and DC voltages areapplied to a pattern of electrodes on the inside wall of a tube, the RFand DC voltages generating an RF multipole field, preferably aquadrupole field, enclosing the filters and an axial DC electric fieldprofile for the two filters, and wherein the tube guides the moving gas.The strength of RF multipole field is adjusted for best and undisturbedcollection of the ions collected.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A to 1D schematically illustrate design (1A and 1B) and potentialand field profiles for the operation (1C and 1D) of an ion mobilityspectrometer according to the state of the art, as described in U.S.Pat. No. 7,838,826 B1 (M. A. Park, 2008). The gas is flowing in tube(11) with parabolic velocity distribution (14). The operation is shownschematically by the profiles of the potential (1C) and the electriccounter-field barrier (1D) and their effect on the gas-driven ions (27)with different cross sections indicated by the size of the dots.

FIG. 2 depicts the operation of an inventive embodiment with two ionmobility low pass filters. A gas flow from left to right blows ions(52-59) with different cross sections against two electric fieldbarriers (50) and (51). The selected ions (55) and (56) are collectedbetween the two barriers.

In FIG. 3, the gas blows from the right-hand site to the left-hand site,and electric forces −E_(z) drive the ions in the direction to the right.(The electric field strength here is negative, because in thisdescription a positive field E_(z) always defines a counter field). Twodifferent field strengths (60) and (61) form two different high passfilters, each separating the ions by their mobilities. The ions (66) and(67) with medium mobility are collected in between the two high passfilters.

In FIG. 4, an ion mobility high pass filter (left-hand side) is combinedwith an ion mobility low pass filter (right-hand side), to select theions (77) and (78), which can pass the two mobility filters in acontinuous ion current and may be analyzed by a mass spectrometer.

FIGS. 5A-5C schematically exhibit, as an example for a first embodimentof the invention, a tube arrangement (FIG. 5A), a DC potential profile(30) (FIG. 5B) and the resulting two DC electric field barriers (31) and(32) (FIG. 5C) forming two consecutive ion mobility low pass filters forthe collection of ions (34) of a predetermined range of mobilitiesbetween the two barriers inside a radial RF quadrupole field.

FIGS. 6A-6C schematically show an example of a second embodiment, withtwo opposite gas flows (14 a) and (14 b) inside the tube halves (11 a)and (11 b) (as shown in FIG. 6A), the potential profile (40) (FIG. 6B),forming the driving electric field (44) in the counteracting gas flowfor the ion mobility high pass filter, and the second field barrier (46)for the ion mobility low pass filter, presented in FIG. 6C. The ions(49) form a continuous ion current with ions of selected mobility.

FIG. 7 presents a special case of the arrangement according to FIG. 2,wherein the maximum E₁ of the first field barrier (90) continues in formof a field plateau with essentially constant electric counter field ofstrength E₁ up to the second field barrier (91) with strength E₂. Ionsof a distinct mobility (96) gathering between the low pass filters canspread over the full plateau, thereby minimizing any influence of spacecharge on the mobility separation. Because of this, many more ions canbe collected without space charge disturbances than in the arrangementof FIG. 2.

DETAILED DESCRIPTION

While the invention has been shown and described with reference to anumber of embodiments thereof, it will be recognized by those skilled inthe art that various changes in form and detail may be made hereinwithout departing from the spirit and scope of the invention as definedby the appended claims.

As mentioned above, the invention provides devices and methods forselecting ions with predetermined mobility. Either many of theseselected ions may be collected and stored for further investigations, orions may be filtered according to their mobility, thus generating aconstant beam of ions with predetermined mobility.

The invention is based on the finding that all ion mobility measuringdevices with electrical forces and counteracting gas flows act either asion mobility high pass or low pass filters, each separating ions intothose which pass the device and those which are held back. It should bekept in mind that ions with higher mobilities as a rule have smallercross sections; ions with lower mobilities have larger cross sections,and ions with larger cross sections experience larger friction forces inthe gas. If the electric force drives the ions against a gas flow, theresult is a mobility high pass filter; if the gas flow drives entrainedions against an electrical barrier, the result is a mobility low passfilter.

The invention provides devices and methods with consecutive mobilityhigh pass and/or low pass filters for the selection of ions within apredetermined range of ion mobilities, either for the collection of manyof these ions in a suitable volume, or for the generation of a constantbeam of ions with predetermined mobility. In some embodiments of theinvention, exactly two consecutive high pass and/or low pass filters areused.

In first embodiments of the invention, the gas flows in one directiononly through two mobility filters, forming either two consecutive ionmobility low pass or two ion mobility high pass filters. These twofilters allow for the collection of ions with selected ion mobilitiesbetween the two filters.

In one of these first embodiments, the gas drives entrained ions againsta first field barrier, keeping back all ions with mobilities μ≧μ₁. Thiscase is schematically illustrated in FIG. 2, showing the disposition ofions (52) to (59) with different mobilities, indicated by differentsizes of the dots representing the ions with their cross sections. Thegas drives the ions (55) to (59), that have passed the first barrier(50) against a second field barrier (51), keeping back the ions (55) and(56) with mobilities μ≧μ₂ and thus keeping back and collecting all ionsof an mobility in the range Δμ between μ₁ and μ₂ with μ₁>μ₂. The ions(57) to (59) with μ<μ₂ pass the second barrier and disappear. To collectthe ions (55) and (56), there has to be an ion storage device betweenthe filters, e.g. by the provision of radial forces to keep the ionswithin the collection volume between the two barriers, such like amultipole field with its centripetally acting pseudopotential. Thesimplest way to generate the storage volume may be an enclosure of bothfilters in an RF multipole device, for instance, in an RF quadrupolesystem. The collected ions (55) and (56) in the mobility range Δμ mayfinally be investigated in more detail, e.g. by a highly resolvedmobility scan using the second mobility filter, or by transferring theseions to a mass spectrometer for the generation and acquisition offragment ion mass spectra.

In another of these first embodiments, the gas flow is directed towardsthe source of ions, forming two high pass filters, in which electricfields of adjustable strength drive the ions (62) to (70) against aconstant flow of gas. This embodiment is symbolically shown in FIG. 3.In the left-hand half of the Figure, a field of strength (60) can onlytransport the ions (66) to (70) against the gas, and in the right-handhalf, the weaker field strength (61) can only the ions (67) to (70)transport further. The ions (66) and (67) of the selected range ofmobilities are collected between the two high pass filters. Again, theions in this collection volume have to be enclosed by a suitable storagedevice.

In a second embodiment, the gas flows in two consecutive filters indifferent directions, thus producing one high pass and one low passfilter. An example is symbolically presented in FIG. 4. If fieldstrengths and gas flows are adjusted correctly, ions (77) and (78) of aselected range of mobilities can pass both filters, thus forming acontinuous current of ions with selected mobilities. In the embodimentshown, gas must be introduced between the two mobility filters,generating two gas flows in two opposing directions. In the firstmobility filter, an electric field of controllable strength (71) isadjusted so that it cannot drive ions (73) to (76) with μ<μ₃ against thegas flow, thus forming a mobility high pass filter for ions (77) to(81), keeping back the ions of low ion mobility. In the second mobilityfilter, an electric field barrier (72) in the gas flow forms a mobilitylow pass filter, and only ions (77) and (78) with mobilities in therange between μ₃ and μ₄ can successfully pass the embodiment. These ions(77) and (78) of predetermined mobility may be further investigated by amass spectrometer. It is even possible to scan this filter function, inorder to investigate ions of more than only one mobility.

By pumping gas from the space between two filters, the direction of thetwo gas flows will be changed, so that, with corresponding potentialprofiles, a first mobility filter acts as a low pass filter, and thesecond as the high pass filter.

Examples for the two embodiments symbolically depicted in FIGS. 2 and 4are now described in more detail, based on the ion mobility spectrometeras described in document U.S. Pat. No. 7,838,826 B1 (M. A. Park, 2008),but, according to the invention, modified to form two consecutive ionmobility filters inside the spectrometer.

One arrangement of the first embodiment of the method is schematicallyillustrated in FIGS. 5A-5C, showing the tube (11) with unidirectionalgas flow (14) in FIG. 5A, the voltage profile (30) in FIG. 5B, and thetwo electric barriers (31) and (32) in FIG. 5C. A pattern of electrodesat the inner wall of the tube generates both the RF quadrupole field andthe DC potential profile for the DC electric field barriers. Theelectric field barriers form two ion mobility low pass filters for ionswith mobilities μ<μ₁ and μ<μ₂, respectively. The ions (33) of highestmobility are held back by the first barrier (31), the ions (35) oflowest mobility pass the second barrier (32), and the selected ions (34)of the mobility range between μ₁ and μ₂ are collected and stored in thequadrupolar RF field of the tube between the two electric barriers (31)and (32) shown in FIG. 5C. These (34) ions may then be investigated inmore detail, e.g. by a mobility measurement with highest resolutionusing the second electric field barrier.

Particularly interesting, however, is an investigation of these storedions (34) by a mass spectrometer (not shown in the figures). The ions(34) may be transferred to a fragmentation cell of the massspectrometer, where the ions may be fragmented by one of the well-knownfragmentation processes, as, for instance, collisionally induceddecomposition (CID) or electron transfer dissociation (ETD). Thefragment ions are then investigated by the mass analyzer of the massspectrometer. The ion mobility device must be arranged between ionsource and analyzer of the mass spectrometer; for a fragmentation,between ion source and fragmentation cell.

An example of an arrangement for the second embodiment is schematicallypresented in FIGS. 6A-6C. Two gas flows (14 a) and (14 b) in oppositedirections have to be generated by supplying gas (29) to the tube (11 a,11 b) at a location near the middle. In FIG. 6C, a first electricdriving field with strength (44) in the counter-flowing gas (14 a) formsan ion mobility high pass filter for ions with mobilities μ>μ₃, and anelectric field barrier (46) generated by the potential profile (40, 41,42 in FIG. 6B) forms an ion mobility low pass filter in the gas flow (14b) for ions with mobilities μ<μ₄, so that ions with selected mobilitiesμ₄-μ₃ can pass continuously the two mobility filters. The two gas flows(14 a) and (14 b) may not have necessarily the same velocity.

In FIG. 6A, the tube (11) is now divided into two parts (11 a) and (11b), and gas (29) is supplied between the two parts, generating the twogas flows (14 a) and (14 b). The potential profile (40, 41, 42 shown inFIG. 6B) produces the driving field (44) for ions against the gas flow(14 a), forming the mobility low pass filter which continuously keepsback the ions (47) of low mobility. The part (42, 43) of the voltageprofile forms the electric field barrier (46, FIG. 6C) of the mobilityhigh pass filter, holding back the ions (48) of highest mobility, andletting pass the ions (49) of the selected mobility range. These ionsform a continuous current of ions, quite different from the phase-wiseion selection of the first embodiment in a volume. The ions of thiscontinuous current may be further analyzed by a mass spectrometer, e.g.by collection and fragmentation of these ions in a fragmentation cell,and analysis of the fragment ions by the analyzer. It has to bementioned, that the ions which are held back in tube (11 a, 11 b) haveto be eliminated in some way or other, either continuously by suitablemeans, or periodically, e.g., by periodically weakening the focusing RFvoltage at the electrodes of the tube. The elimination is supported bythe space charge of these ions.

Some particularly favorable methods are based on an arrangement of twolow pass filters with a field distribution as presented in FIG. 7. Thefield barrier maximum of the first low pass filter (90) with counterfield strength E₁ continues as a plateau with essentially constant fieldstrength up to the second low pass filter (91) with maximum fieldbarrier strength E₂. The field strengths E₁ and E2 can be adjustedindependently. If the difference ΔE=E₁−E₂ is small, ions (56) of narrowmobility range will be collected, and these ions spread over the wholeplateau. The effect on space charge thus is minimized; much more ionscan be collected without disturbing influences of the space charge inthis arrangement than can be collected in the arrangement of FIG. 2. Theresolution of this selection process is by far larger than R_(mob)=100.It is possible collect ions with a chosen mobility, separated from ionswith a mobility which is only different by about one percent. The ionscollected can then be transferred to a detector or an analyzing device,such as a mass spectrometer, by changing the electric field of at leastone of the low pass filters, for example by decreasing the maximum fieldstrength E₂ of the second low pass filter, or by increasing the heightof the first low pass filter E₁ including the field strength of theplateau. It is advantageous to stop ions from entering the region of themobility filters before starting the transfer of ions, for example bygenerating a further DC barrier upstream of the first mobility filter.Without deteriorating the resolution of the separation by space charge,the number of ions for this analysis can be considerably larger than thenumber of ions which can be collected by the arrangement of FIG. 2.

This arrangement with two low pass filters connected by a field strengthplateau can also be used to measure mobility spectra with adjustableresolution by stepwise alteration of the field barrier maxima E₁ and E₂.The resolution is adjusted by the size of the difference ΔE and the stepwidth. With very small values ΔE, a high mobility resolution by farlarger than R_(mob)=100 can be achieved. Thus it is possible, toinvestigate at least parts of the mobility spectrum with high resolutionand high sensitivity.

The invention also comprises the corresponding selection device for ionsof predetermined mobility, with a tube (11) with four rows of electrodes(17), (18) as shown in FIG. 1A along the inner wall, an RF generator tosupply the rows of electrodes alternately with the phases of an RFvoltage to generate the quadrupolar RF field for the collection of theions in the tube axis, a network of resistors (not shown) connected tothe electrodes (17) and (18), at least two DC voltage generators (notshown), connected to the network of resistors, generating potentialprofiles with at least two electric field barriers inside the tube, andmeans for generating at least one laminar gas flow inside the tube.

In a first embodiment of the selection device, two electric fieldbarriers form, for ions driven by a given unidirectional gas flow, twosubsequent ion mobility low pass filters for ions with mobilities μ<μ₁and μ<μ₂ respectively. A second embodiment comprises means for thegeneration of two gas flows in opposite directions, and means forgenerating the potential profiles for a first ion mobility high passfilter for ions with mobilities μ>μ₃ and a second ion mobility low passfilter for ions with mobilities μ<μ₄.

The ion mobility selection devices are preferably mounted in a massspectrometer, in a position between ion source and mass analyzer. Iffragment spectra should be obtained, the ion mobility selection deviceshould be mounted between ion source and fragmentation cell of the massspectrometer.

In all embodiments, the parameters of the instrument downstream andupstream of the mobility filters, in particular, the strength of the RFmultipole field confining the ions in radial direction at and/or inbetween the mobility filters, may be adjusted for the collection of amaximum of ions, or for an optimization of other features of the method.Furthermore, the RF multipole field strength may adapted according tothe charge-related mass m/z of the ions to be collected such that theyare radially confined near the axis and therefore experience a nearlyconstant velocity despite of the parabolic velocity profile of the gasflow.

As already described above, the methods and devices according to thepresent invention can be used to acquire mobility spectra or coupledmobility/mass spectra, respectively. A mobility spectrum can be acquiredby repeated adjustment of the mobility filters, such that differentmobility ranges of ions being collected between the mobility filters orpassing the mobility filters are scanned. A first measured mobilityspectrum with low mobility resolution may serve as an overview spectrumwhich is used to determine regions of interest being scanned thereafterwith high mobility resolution. A mobility spectrometer as described inU.S. Pat. No. 7,838,826 B1 (M. A. Park, 2008) may be utilized to acquirean overview spectrum.

The embodiments can be varied in many ways by any specialist in thefield, e.g. by reversing the gas flow directions in the secondembodiment. The gas used for the second embodiment may also replace thegas which transports the ions into the ion funnel in front of the tube.The replacing gas may not be of the same type as the transportation gas.

What is claimed is:
 1. A method for filtering ions having ion mobilitieswithin a predetermined ion mobility range μ₁>μ>μ₂ and entrained in astream of moving gas, comprising: (a) filtering the ions with a firstand a second ion mobility low pass filter located consecutively in themoving gas stream with the second filter being downstream of the firstfilter, each filter formed by the action of the moving gas having afriction force on the ions and a counter-directed electric field on theions, an electric field of the first filter blocking the passage of ionswith a mobility of μ≧μ₁ and an electric field of the second filterblocking the passage of ions with a mobility of μ≧μ₂, where μ₂<μ₁,wherein the counter-directed electric field of the first filter and thecounter-directed electric field of the second filter are each stationaryalong an axis parallel to the direction of the flow of the gas; (b)collecting ions in said predetermined ion mobility range in a spacebetween the two filters; and (c) transferring collected ions to one of adetector and an analyzing device by changing the electric field of atleast one of the low pass filters.
 2. The method according to claim 1,wherein ions are prevented from entering the two ion mobility low passfilters before starting step (c).
 3. The method according to claim 2,wherein ions are prevented from entering the two ion mobility low passfilters by generating an electric DC barrier upstream of both ionmobility low pass filters.
 4. The method according to claim 2, furthercomprising repeatedly collecting and transferring ions of differentmobilities in order to acquire an ion mobility spectrum.
 5. The methodaccording to claim 4, wherein ions in the two ion mobility low passfilters are confined in direction radial to the gas stream direction byfirst and second RF multipole fields and wherein step (b) comprisesconfining the ions in direction radial to the gas stream direction by athird RF multipole field located between the two ion mobility low passfilters and adjusting the field strength of the first, second and thirdRF multipole fields to collect a maximum of ions of the differentmobilities.
 6. The method according to claim 1, wherein each of the twoion mobility low pass filters comprises an electric field barrier, andwherein the maximum field strength of the electric field barrier in thefirst ion mobility low pass filter is continued as a plateau ofessentially constant field strength up to the electric field barrier inthe second ion mobility low pass filter, the electric field barrier inthe second ion mobility low pass filter having a maximum field strengthhigher that the maximum field strength of the electric field barrier inthe first ion mobility low pass filter.
 7. The method according to claim6, wherein ions are prevented from entering the two ion mobility lowpass filters before starting step (c).
 8. The method according to claim7, further comprising repeatedly collecting and transferring ions ofdifferent mobilities in order to acquire an ion mobility spectrum. 9.The method according to claim 8, wherein the resolution of the ionmobility spectrum is adjusted by adjusting a difference in fieldstrength between the first and second field barrier.
 10. The methodaccording to claim 9, wherein the difference in field strength islowered to collect ions of a narrow mobility range and to increaseresolution.
 11. The method according to claim 6, wherein step (c)comprises one of decreasing the maximum field strength of the secondelectric field barrier and increasing the height of the first electricfield barrier including the field strength of the plateau.
 12. Themethod according to claim 1, wherein the analyzing device is a massspectrometer.
 13. An ion mobility filter comprising: a tube having aninner wall with a pattern of electrodes along the inner wall, an RFgenerator that supplies the pattern of electrodes with a two phase RFvoltage so that a multipolar RF field forms inside the tube, a networkof resistors connected to the pattern of electrodes, at least one DCvoltage generator, connected to the network of resistors, for generatingaxial potential profiles forming a first and a second electric fieldbarrier inside the tube to form two low pass ion mobility filters in thetube, wherein the first DC electric field barrier blocks the passage ofions with a mobility of μ≧μ₁ and the second DC electric field barrierblocks the passage of ions with a mobility of μ≧μ₂, where μ<μ₁ andwherein the maximum field strength up to the second field barrier havinga maximum field strength higher than the maximum field strength of thefirst field barrier, and a gas source that generates a laminar gas flowinside the tube driving ions first against the first electric fieldbarrier and subsequently against the second electric field barrier,wherein the first DC electric field barrier and the second DC electricfield barrier are each stationary along an axis parallel to thedirection of the flow of the gas.
 14. The ion mobility filter of claim13, wherein a quadrupolar RF field is formed inside the tube.
 15. Theion mobility filter of claim 13, further comprising a first control thatacts on the DC voltage generator to adjust the field strength of thefirst electric field barrier and the plateau.
 16. The ion mobilityfilter of claim 14, further comprising a second control that acts on theDC voltage generator to adjust the field strength of the second electricfield barrier.
 17. The ion mobility filter of claim 16, furthercomprising a switchable electric DC barrier upstream of the first ionmobility low pass filter.